The specific aim of this research is to develop mathematical models corroborated by clinical data for describing oxygen transport in human tumors. The models will be used to gain insight in to the role of oxygen in the response of tumors to radio therapy and chemotherapy. They may also predict methods by which oxygen in tumors can be manipulated to optimize the therapeutic effect. Thus, this research in the long term may contribute significantly to the formulation of new and improved protocols for enhancing these therapies in cancer treatment. The researchers will formulate transient mathematical models based on physico-chemical principles. The analysis will employ the results of a new clinical procedure for the direct measurement of tissue oxygen tension in-vivo in human tumors via a CT-guided probe developed and performed at the Fox Chase Cancer Center. Already over fifty different lesions have been examined, and this unique data base is being developed further. These clinical data will be used in conjunction with state-of-the-art facilities and techniques in computer-aided engineering design to develop the mathematical models. Menu-driven interactive graphics-based software will be used to evaluate the models. Using these novel clinical and enginneering techniques both steady-state and transient multi-region models will be developed. Steady-state models corroborated with clinical data can be used to predict new oxygen tension levels within tumors when body pO2 levels are increased (i.e., by hyperbaric oxygen or blood transfusions). Solutions to the time-dependent version of these models can be used to predict the time required to raise PO2 throughout the tumor and thus increase the response to radiation. Both of these could have considerable impact on the clinical use of oxygen (under normal pressure or hyperbaric conditions) to increase the radiosensitivity of human tumors. As an adjunct to these studies the effect of regional differences in tumor PO2 on tumor pH will be investigated to understand the role of PO2 in regional tumor metabolism since hypoxia should result in glycolytic metabolism and therefore acidosis. In addition the effects of point sources of oxygen and convective flow within tumors will be investigated. These studies will have direct bearing on chemical infusion techniques for increasing oxygen levels in tumors.